Four histamine receptors (H-1, H-2, H-3, H-4) have been identified, all of which are G protein-coupled receptors. The four different receptors are expressed on various cell types and exert their effects through different intracellular signaling mechanisms, which may in part be related to the diverse effects of histamine in different cells, tissues and organs.
The human histamine H-4 receptor is active constitutively, as is also the case with human histamine H-1, H-2 and H-3 receptors. Thus, like all other histamine receptor inhibitors, histamine H-4 receptor inhibitors are inverse agonists on the human histamine receptors.
Several potent and selective histamine H-4 receptor ligands have been described, such as for example JNJ 7777120, JNJ 10191584 and 4-methylhistamine. Such ligands will bind to all human histamine H-4 receptors, wherever those receptors are expressed in the body, such as for example, in bone marrow and white blood cells. The disadvantage of these compounds is that they act with high potency inhibiting histamine H-4 receptors throughout the body, increasing the likelihood of unwanted systemic side effects.
What is needed are improved methods of selectively treating medical conditions associated with histamine H-4 receptors at the biophases of those conditions.